Process for production of enantiomerically pure 2,2,4-trisubstituted 1,3-dioxolanes

ABSTRACT

Enantiomer-free 2,2,4-trisubstituted 1,3-dioxolanes of the general formula: ##STR1## wherein R 1  and R 2  are either the same and are (a) hydrogen or 
     (b) alkyl groups with 1 to 4 C atoms or 
     (c) aryl groups or 
     (d) arylalkyl groups 
     or R 1  and R 2  together are a 1,4-butanediyl or 1,5-pentanediyl group, and X is either a hydroxy group or, with the assumption that R 1  and R 2  are not aryl groups, NHR 3  wherein R 3  is alkyl with 1 to 8 C atoms or aryl, are produced by electrolysis of a substated theronic acid or erythornic acid or a salt thereof into a substituted 1,3-dioxolane-4-carbaldehyde. The substituted 1,3-dioxolane-4-carbaldehyde is converted by reduction or reductive amination, without being ioslated, into the enantiomer-free 2,2,4-trisubstituted 1,3-dioxolane. A substantial advantage of the electrochemical process is that only carbon dioxide and hydrogen are produced which escape by themselves as gases from the electrolyte.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to a process for the production ofenantiomerically pure 2,2,4 -trisubstituted 1,3-dioxolanes.

2. Background Art

Enantiomerically pure 2,2,4-trisubstituted 1,3-dioxolanes of the generalformula: ##STR2## wherein X is OH or X is NHR³, as derivatives ofglycerin or 3-amino-1,2-propanediol, are extremely valuable chiralbuilding blocks for stereospecific syntheses of natural products and ofother optically active compounds, as, for example, pharmaceutical activeingredients. Some examples of these uses are the syntheses of(R)-4-amino-3-hydroxybutyric acid (GABOB) [J. Am. Chem. Soc. 102, 6304(1980)], L carnitine (European Published Patent Application No.0,060,595), acyclovir analogs [J. Med. Chem. 28, 926 (1985)] orbeta-blockers (German OS No. 2810732).

Although some of these 1,3-dioxolanes, namely, the acetonides ofglycerol (R¹ =R² =CH₃, X=OH), and some ethers and esters derived fromthem (X=OCH₂ C₆ H₅, O-tosyl) are already commercially available, thestill very high price of these compounds prevents their use to a largeextent. The numerous production processes known so far start fromexpensive feedstock (L-serine, L-arabinose) and/or expensive reagentsused [lead(IV) acetate, NaIO₄, bismuth compounds, among others] and,therefore, do not allow production on an industrial scale and atattractive prices for reasons of costs.

A new process for the production of(S)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (L-glyceraldehydeacetonide), (European Published Patent Application No. 0,143,973), fromwhich the corresponding hydroxy compound can be obtained by reduction,for example, with sodium tetrahydridoborate, starts from3,4-O-isopropylidene-L-threonic acid, which is degraded withhypochlorous acid or hypochlorite in an acid medium to theL-glyceraldehyde acetonide. Although 3,4-O-isopropylidene-L-threonicacid starting from L-ascorbic acid is easily available and thehypochlorite solution is a cheap chemical, such process still has someserious drawbacks:

The commercially available hypochlorite solutions vary in content andare not completely stable.

The free hypochlorous acid formed during the conducting of the processis still not very stable and partially decomposes, and, thus, more thanthe theoretically required amount is consumed.

An excess of hypochlorite still present after the course of theoxidation must be destroyed by the addition of a reduction agent. Thus,other extraneous materials are introduced into the reaction mixture.

The hypochlorite solution is very corrosive and requires acorrespondingly resistant material for the apparatus used.

The hypochlorite solution used already contains large amounts ofchloride, and further chloride is formed in the reaction. This totalchloride amount must finally be disposed of; moreover, working up of thereaction mixture is possibly disturbed by the high salt concentration.

Performing the oxidation in an acid solution in the case of sensitiveketals and especially acetals can lead to hydrolysis of the ketal oracetal function and in these cases can make the process unusable.

BROAD DESCRIPTION OF THE INVENTION

The main object of the invention is to provide a process which does notexhibit such drawbacks and can be used for the production of amultiplicity of different substituted enantiomerically pure2,2,4-trisubstituted 1,3-dioxolanes of general formula I set out herein.The main object of the invention is achieved by the process of theinvention.

The invention involves a process for the production of enantiomericallypure 2,2,4-trisubstituted 1,3-dioxolanes of the general formula:##STR3## wherein R¹ and R² are either the same and are (a) hydrogen or

(b) alkyl groups with 1 to 4 C atoms or

(c) aryl groups or

(d) arylalkyl groups

or R¹ and R² together are a 1,4-butanediyl or 1,5-pentanediyl group, andX is either a hydroxy group or, with the assumption that R¹ and R² arenot aryl groups, NHR³ with R³ being alkyl with 1 to 8 C atoms or aryl,characterized in that, depending on the desired configuration, acorresponding substituted threonic acid or erythronic acid of thegeneral formula: ##STR4## or a salt thereof is converted by electrolysisinto the correspondingly substituted 1,3-dioxolane-4-carbaldehyde of thegeneral formula: ##STR5## The corresponding substituted1,3-dioxolane-4-carbaldehyde without isolating it, is converted byreduction or reductive amination into the enantiomerically pure2,2,4-trisubstituted 1,3-dioxolane according to formula I.

The oxidative decarboxylation of a threonic acid or erythronic acid ofthe general formula: ##STR6## produces the corresponding glyceraldehydederivative in good yield by electrolysis with the configuration on thebeta-carbon atom being maintained. A substantial advantage of thiselectrochemical process is that, besides the desired product, onlycarbon dioxide and hydrogen are produced, which escape by themselves asgases from the electrolyte. Also, no excess of an oxidation agent, whichwould have to be eliminated after termination of the reaction, canoccur.

Radicals R¹ and R² can be hydrogen or lower alkyl groups, preferablymethyl or ethyl, especially methyl, or aryl groups, especially phenyl,or arylalkyl groups, especially benzyl. Further, R¹ and R² together canform a 1,4-butanediyl or especially 1,5-pentanediyl group, so thattogether with the carbon atom of the ketal function a five- orsix-membered ring is produced.

Electrolysis suitably takes place in an aqueous medium, such as, amixture of water with lower alcohols, acetonitrile, dimethylformamide,dimethyl sulfoxide, hexamethylphosphoric acid triamide ortetrahydrofuran, but preferably in water without additional solvent. Anoble metal, such as, platinum, gold or iridium, or graphite can be usedas the electrode material for the two electrodes but graphite ispreferably used for the anode. An undivided cell, in which the solutionis continuously circulated, is suitably used as the cell.

On a laboratory scale, performance of the electrolysis for example isalso possible on platinum electrodes in a beaker, and the solution isstirred or thoroughly mixed with a rotating electrode. The currentdensity is suitably 0.1 to 320 mA/cm², preferably 2 to 80 mA/cm² ; theelectrolysis is preferably performed with a constant current. Normally 2to 2.8 faraday/mol is consumed up to complete reaction. The temperatureduring electrolysis is suitably 5° to 90° C., preferably 10° to 70° C.

The pH of the solution during electrolysis is suitably between 4 and 10and is kept in this range by the addition of acid, preferably sulfuricacid. The electrolysis is preferably performed at a pH of 6 to 7. Theconcentration of threonic acid or erythronic acid derivative duringelectrolysis is suitably between 0.5 and 25 percent, preferably 5 to 15percent.

As the initial material preferably L-threonic acid or D-erythronic acidderivatives are used, which are produced from the correspondingL-ascorbic acid or D-isoascorbic acid (D-erythronic acid) derivatives ofthe general formula ##STR7## wherein R¹ and R² have the above-mentionedmeanings, by oxidative cleavage, preferably with aqueous hydrogenperoxide in the presence of calcium carbonate (European Published PatentApplication No. 0,111,326).

The L-threonic acid and D-erythronic acid derivatives in the last namedproduction process accumulate as aqueous solutions of their calciumsalts; in addition slightly soluble calcium oxalate is produced. Inelectrolysis of the calcium salts, a precipitation of calcium carbonateor calcium hydroxide on the electrodes occurs. Therefore, the calciumsalts are suitably converted into an alkali salt or into the free acidsby treatment with a cation exchanger. Then the free acid can beconverted with a suitable base, preferably an alkali hydroxide or atertiary amine, such as, triethylamine, into a salt suitable forelectrolysis. The conversion of the calcium salt into the free acids canalso take place by the calcium precipitating in the form of a slightlysoluble salt. This can be achieved, for example, by the addition ofsulfuric acid, which, with calcium, forms slightly soluble calciumsulfate.

But it has proven especially favorable to perform the oxidation ofL-ascorbic acid or D-isoascorbic acid derivatives in the presence of analkali carbonate, preferably sodium carbonate. Thus, the resultantL-threonic acid or the D-erythronic acid is obtained from the beginningin the form of alkali salt, while the calcium of the calcium carbonate,also added, binds the resultant oxalic acid only in the form of theslightly soluble calcium oxalate. The alkali carbonate is suitably addedin an amount of 0.5 to 2 mol (relative to 1 mol of L-ascorbic acid orD-isoascorbic acid derivative).

The glyceraldehyde derivative obtained by electrolysis can be isolatedby the usual extraction process and purified by distillation in avacuum. But since glyceraldehyde derivatives are only slightly stable,it is advisable not to isolate them but to react them further directlyin the reaction mixture. In the process according to the invention, thisreaction takes place by reduction of the aldehyde function to thehydroxymethyl group or by reduction in the presence of a primary amine,preferably a lower alkyl amine, such as, isopropylamine, with formationof a secondary amino group.

The reduction is preferably performed by catalytic hydrogenation,especially on Raney nickel or palladium catalysts; reduction to thehydroxymethyl group can also take place especially with sodiumtetrahydridoborate. It is also possible to convert the glyceraldehydederivative into a more stable compound by another reaction, for example,the formation of a Schiff base with an amine (European Published PatentApplication Nos. 0,120,289 and 0,143,973).

EXAMPLE 1 5,6-O-isopropylidene-L-ascorbic acid

10.0 g (55 mmol) of L-ascorbic acid was added to a solution of 1 ml ofacetyl chloride in 40 ml of acetone. The heterogeneous mixture wasstirred for 3 hours at room temperature and then 8 hours at 0° to 5° C.The product was filtered off, washed twice with 5 ml of cold acetoneeach time and dried. The yield was 9.65 g (81.1 percent). The producthad a melting point of 223° to 226° C. The product had the followingproperties:

[α]_(D) ²⁰ =+10.5° (c=5, methanol)

H¹ -NMR: (CD₃ OD, 300 MHz) δ: 1.34 (s,3H); 1.37 (s, 3H); 4.04 (dd,J=8.5/6.5 Hz, 1H, H-C(6)); 4.17 (dd, J=8,5/7 Hz, 1H, H-C(6)); 4.33 (ddd,J=7/6.5/3 Hz, 1H, H-C(5)); 4.67 (d, J=3 Hz, 1H, H-C(4)).

EXAMPLE 2 5,6-O-cyclohexylidene-D-isoascorbic acid

In a 200-ml three-neck flask, 4.45 g (45.2 mmol) of cyclohexanone, 7.05g (47.5 mmol) of triethyl orthoformate, 0.04 g of p-toluenesulfonic acid(monohydrate), 4.15 g (90 mmol) ethanol and 95 ml of ethyl acetate wereheated to 100° C. and kept at this temperature for 1 hour (reflux).Thus, 1,1-diethoxycyclohexane was formed. Then 4.0 g (22.7 mmol) ofD-isoascorbic acid was added and the first heterogeneous mixture wasrefluxed for 5 hours, and a clear solution was formed. Then 2 g ofaluminum oxide was added, the suspension was stirred for 1 more hour atroom temperature and filtered over Celite®, which was rewashed threetimes with ethyl acetate. The filtrate was concentrated by evaporationat 35° C./30 mbars to 20.5 g, and a viscous pulp was formed. The productwas completely precipitated by addition of 20 ml of hexane, filtered offand dried. The yield was 5.05 g (86.8 percent). The product had amelting point: 177° to 178.5° C. The product had the followingproperties:

¹ H-NMR: (Acetone-d₆, 300 MHz) δ: 1.30-1.50 (m, 2H); 1.50-1.70 (m, 8H);2.97 (m, 2H, OH); 3.77 (dd, J=8.5/6 Hz, 1H, H-C(6)); 4.01 (dd, J=8.5/7Hz, 1H, H-C(6)); 4.42 (ddd, J=7/6/4 Hz, 1H, H-C(5)); 4.84 (d, J=4 Hz,1H, H-C(4)).

EXAMPLES 3 to 8

The following ketals were produced analogously to Example 2.

EXAMPLE 3 5,6-O-cyclopentylidene-D-isoascorbic acid

The yield was 61 percent. The product has the following properties:

¹ H-NMR: (CD₃ OD, 300 MHz) δ: 1.60-2.05 (m, 8H); 3.73 (dd, J=8.5/6 Hz,1H, H-C(6)); 3.91 (dd, J=8.5/7.5 Hz, 1H, H-C(6)); 4.36 (ddd, J=7.5/6/3Hz, 1H, H-C(5)); 4.82 (d, J=Hz, 1H, H-C(4)).

EXAMPLE 4 5,6-O-(1-ethylpropylidene)-D-isoascorbic acid

The yield was 57 percent. The product had the following properties:

¹ H-NMR: (CD₃ OD, 300 MHz) δ: 0.89 (t, 3H); 0.91 (t, 3H); 1.61 (q, 2H);1.69 (q, 2H); 3.75 (t, J=7 Hz, 1H, H-C(6)); 3.99 (t, J=7Hz, 1H, H-C(6));4.45 (td, J=7/3 Hz, 1H, H-C(5)); 4.88 (d, J=3 Hz, 1H, H-C(4)).

EXAMPLE 5 5,6-O-isopropylidene-D-isoascorbic acid

The yield was 41 percent. The product had the following properties:

¹ H-NMR: (CD₃ OD, 300 MHz) δ: 1.35 (s, 3H); 1.42 (s, 3H); 3.78 (dd,J=8.5/6.5 Hz, 1H, H-C(6)); 4.00 (dd, J=8.5/7 Hz, 1H, H-C(6)); 4.44 (ddd,J=7/6.5/4 Hz, 1H, H-C(5)); 4.83 (d, J=4 Hz, 1H, H-C(4)).

EXAMPLE 6 5,6-O-cyclohexylidene-L-ascorbic acid

The yield was 67 percent. The product had the following properties:

¹ H-NMR: (CD₃ OD, 300 MHz) δ: 1.30-1.48 (m, 2H); 1.48-1.65 (m, 8H); 4.02(dd, J=8/6.5 Hz, 1H, H-C(6)); 4.16 (dd, J=8/7 Hz, 1H, H-C(6)); 4.31(ddd, J=7/6.5/3 Hz, 1H, H-C(5)); 4.65 (d, J=3 Hz, 1H, H-C(4)).

EXAMPLE 7 5,6-O-cyclohexylidene-L-ascorbic acid

The yield was 73 percent. The product had the following properties:

¹ H-NMR: (CD₃ OD, 300 MHz) δ: 1.55-1.85 (m, 8H); 4.00 (dd, J=8.5/6 Hz,1H, H-C(6)); 4.10 (dd, J=8.5/7 Hz, 1H, H-C(6)); 4.26 (ddd, J=7/6.5/3 Hz,1H, H-C(5)); 4.66 (d, J=3 Hz, 1H, H-C(4)).

EXAMPLE 8 5,6-O-(1-ethylpropylidene)-L-ascorbic acid

The product has the following properties:

¹ H-NMR: (CD₃ OD, 300 MHz) δ: 0.80-0.95 (m, 6H); 1.55-1.70 (m, 4H); 4.00(t, J=7 Hz, 1H, H-C(6)); 4.18 (t, J=7 Hz, 1H, H-C(6)); 4.32 (td, J=7/3Hz, 1H, H-C(5)); 4.69 (d, J=3 Hz, 1H, H-C(4)).

EXAMPLE 9 Calcium-3, 4-O-isopropylidene-L-threonate

In a 200-ml three-neck flask, 8.0 g (80 mmol) of calcium carbonate wassuspended at room temperature in 100 ml of water and 8.65 g (40 mmol) of5,6-O-isopropylidene-L-ascorbic acid was added within 30 minutes byportions. After cooling to 5° C., 18.15 g of hydrogen peroxide (30percent solution in water, 160 mmol) was added within 2 hours, and thetemperature was kept below 20° C. The heterogeneous mixture was stirredfor 2 more hours at room temperature and for 30 minutes at 40° C. and,after addition of 2 g of activated carbon, was heated in 1 hour to 85°C. The resulting calcium oxalate and the activated carbon were filteredover Celite® and the filtrate was concentrated by evaporation to 50 g.The product was precipitated by addition of 60 ml of acetone. The yieldwas 6.2 g (77.4 percent) of calcium-3,4-O-isopropylidene-L-threonate 1/4H₂ O. The melting point of the product was greater than 250° C. Theproduct had the following property:

[α]_(D) ²⁰ =+21.5° (c=1, H₂ O)

EXAMPLE 10 Calcium-3,4-O-cyclohexylidene-D-erythronate

18.15 g of hydrogen peroxide (30 percent solution in water, 1.60 mmol)was added to a suspension of 8.0 g (80 mmol) of calcium carbonate and10.2 g (40 mmol) of 5,6-O-cyclohexylidene-D-isoascorbic acid in 150 mlof water within 2 hours, and the temperature was kept below 20° C. Theheterogeneous mixture was stirred for 2 more hours at room temperatureand for 45 minutes at 40° C. and, after addition of 2 g of activatedcarbon, was heated for 1 hour to 90° C. The resulting calcium oxalateand the activated carbon were filtered over Celite® and the filtrate wasconcentrated by evaporation to 52.5 g. The product was precipitated byinstillation of 60 ml of ethanol. The yield was 8.4 g (86 percent) ofcalcium-3,4-O-cyclohexylidene-D-erythronate 1/2 H₂ O. The melting pointof the product was greater than 250° C. The product had the followingproperty:

[α]_(D) ²⁰ =+18.8° (c=1, ethanol)

EXAMPLE 11 (R)-2,2-dimethyl-1,3-dioxolane-4-methanol fromcalcium-3,4-o-isopropylidene-L-threonate (electrolysis in the presenceof triethylamine)

10.0 g of sulfuric acid (50 percent, 50 mmol) was instilled in asolution of 23.8 g of calcium-3,4-O-isopropylidene-L-threonate (82percent, 100 mmol) in 220 ml of water. Then the pH was 1.95 and theheterogeneous mixture was stirred for 10 more minutes at 0° to 5° C. Theprecipitated calcium sulfate dihydrate was filtered off and washed twicewith 10 ml of water each time. The filtrate was mixed with 6.2 g (60mmol) of triethylamine and electrolyzed in an undivided electrolysiscell of 250 ml in volume on graphite electrodes at 15° to 20° C. and aconstant current of 1.0 A for 6.5 hours. The pH, which at the end ofelectrolysis was 8.0 to 8.5, was brought to 7 to 8 by addition of 15 gof disodium hydrogenphosphate (dodecahydrate). The mixture was cooled to0° C., mixed by portions within 1.5 hours with 7.8 g (200 mmol) ofsodium tetrahydridoborate, stirred for 7 hours more at 20° C. and thenfiltered. The filtrate was extracted six times with 200 ml of ether, theorganic phases were dried over sodium sulfate and concentrated byevaporation. The residue was distilled at 24 mbars over potassiumhydroxide. The yield was 6.95 g (52 percent). The product had a boilingpoint of 85° to 87° C./24 mbar. The following data concerns the product:

[α]_(D) ²⁰ =-15.3° (neat)

Content 98.8 percent (GC).

EXAMPLE 12 (R)-2,2-dimethyl-1, 3-dioxolane-4-methanol from5,6-O-isopropylidene-L-ascorbic acid (oxidation and electrolysis in thepresence of sodium carbonate).

A mixture of 10.0 g (100 mmol) of calcium carbonate and 15.9 g (150mmol) sodium carbonate was added by portions to a solution of 21.6 g of5,6-O-isopropylidene-L-ascorbic acid (95 percent, 95 mmol) in 250 ml ofwater within 15 minutes. The heterogeneous mixture was stirred for 1more hour at room temperature and then cooled to 10° C. Then 44.5 g ofhydrogen peroxide (30 percent solution in water, 400 mmol) was instilledwithin 1 hour, and the temperature was kept below 20° C. The mixture wasstirred one more hour at room temperature and 1 hour at 40° C., thenmixed by portions with 4 g of activated carbon and stirred for 1 hourmore at 75° C. After cooling to 50° C., the mixture was filtered overCelite®, the filtrate was cooled in a thermostated beaker to 15° C. andadjusted to pH 6.5 by addition of sulfuric acid and kept at this pHduring electrolysis. The electrolysis took place in tube (d=3 cm) with 2cathodes and 2 anodes made of graphite (d=0.5 cm, l=24 cm) at a currentof 2.2 A, and the solution was continuously circulated by a pump. Atotal of 2.5 faraday/mol was consumed. After electrolysis the pH wasadjusted to 7 to 8 by addition of 15 g of disodium hydrogenphosphate(dodecahydrate), the mixture was cooled to 0° C. and within 1.5 hourswas mixed by portions with 7.8 g (200 mmol) of sodiumtetrahydridoborate. Then the heterogeneous mixture was stirred for 4more hours at 20° C. and then filtered. The filtrate was extracted sixtimes with 100 ml of ethyl acetate each time and the raw productobtained by concentrated by evaporation was distilled in a vacuum. Theyield was 7.5 g (56.4 percent). The following data concerns the product:

[α]_(D) ²⁰ =-15.12° (neat)

Content: 99.3 percent (GC).

EXAMPLE 13 (R)-2,2-dimethyl-1,3-dioxolane-4-methanol from5,6-O-isopropylidene-L-ascorbic acid (electrolysis on Pt electrodes)

As described in Example 12, 9.1 g of 5,6-O-isopropylidene-L-ascorbicacid (95 percent, 40 mmol) was oxidized with hydrogen peroxide in thepresence of calcium carbonate and sodium carbonate. Electrolysis of theresulting solution of sodium-3,4-O-isopropylidene-L-threonate wasperformed at 15° C. in a thermostated beaker. A rotating (2000 l/minute)platinum disk (A=3 cm²) was used as anode, which at the same timeperformed the thorough mixing of the solution. A platinum wire gauze(A=6.2 cm²) was used as cathode. A constant current of 0.6 A up to anamount of electricity of 2.5 faraday/mol was conducted through thesolution. The other steps took place as described in Example 12. Theyield was 2.0 g (37.4 percent). The product had a boiling point of 75°to 77° C./12 torr. The following data concerns the product:

[α]_(D) ²⁰ =-15.3° (neat)

Content: 99.1 percent (GC)

EXAMPLE 14 (S)-1,2-O-cyclohexylideneglycerol fromcalcium-3,4-O-cyclohexylidene-D-erythronate

A solution of 24.8 g of calcium-3,4-O-cyclohexylidene-D-erythronate (95percent, 100 mmol; produced according to example 10) in 160 ml ofmethanol was added to a column of 500 g of Dowex® 50W (protonated form)and eluted with 1.5 l of methanol. The elute was concentrated byevaporation to 120 g and mixed with a solution of 6.2 g (60 mmol) oftriethylamine in 100 ml of water. The other steps were performed asdescribed in Example 11. The yield was 6.0 g (35 percent). The producthad a boiling point of 87° to 89° C./1 torr, 137° C./17 torrs. Thefollowing data concerns the product:

[α]_(D) ²⁰ =+7.3° (c=2, methanol)

¹ H-NMR: (CDCl₃, 300 MHz) δ: 1.30-1.50 (m, 2H); 1.50-1.70 (m, 8H); 3.04(t, J=6 Hz, 1H, OH); 3.59 (ddd, J=11.5/6/5.5 Hz, 1H, H-C(3)); 3.70 (ddd,J=10/6/4.5 Hz, 1H, H-C(3)); 3.77 (dd, J=8/6.5 Hz, 1H, H-C(1)); 4.03 (dd,J=8/6.5 Hz, 1H, H-C(1)); 4.23 (tdd, J=6.5/5.5/4 Hz, 1H, H-C(2)).

Content: 96.6 percent (CG)

EXAMPLE 15 (S)-1,2-O-cyclohexylideneglycerol from5,6-O-cyclohexylidene-D-isoascorbic acid

A solution of 25.7 g of 5,6-O-cyclohexylidene-D-isoascorbic acid (95percent; 95 mmol; produced according to Example 2) in 250 ml of waterwas oxidized in the presence of calcium carbonate and sodium carbonatewith hydrogen peroxide as described in Example 12 and then electrolyzed.The yield was 5.7 g (34.7 percent). The following data concerns theproduct:

[α]_(D) ²⁰ =+7.4° (c=5, methanol)

Content: 98.7 percent (GC)

EXAMPLE 16 (S)-1,2-O-cyclocpentylideneglycerol from5,6-O-cyclopentylidene-D-isoascorbic acid.

A mixture of 4.0 g (40 mmol) of calcium carbonate and 6.4 g (60 mmol) ofsodium carbonate was added by portions within 10 minutes to a solutionof 10.2 g of 5,6-O-cyclopentylidene-D-isoascorbic acid (95 percent, 40mmol; produced according to Example 3) in 150 ml of water. Theheterogeneous mixture was stirred for 1 more hour at room temperatureand then cooled to 10° C. Then within 1 hour 18.15 g of hydrogenperoxide (30 percent solution in water, 160 mmol) was instilled so thatthe temperature remained below 20° C. The mixture was stirred for 1 hourmore at room temperature and for 1 hour at 40° C. and then mixed within30 minutes with 2 g of activate carbon. Then it was stirred for 1 hourmore at 85° C. and, after cooling to 50° C., was filtered over Celite®.The filtrate was cooled to 15° C. in a thermostated beaker and broughtto a pH of 6.5 by addition of sulfuric acid and was kept at this pHduring electrolysis. Electrolysis was performed in a tube (d=3 cm) on 2cathodes and 2 anodes of graphite (d=0.5 cm, l=7 cm) with 1.6 A and atotal of 2.5 faraday/mol was consumed, and the solution was continuouslycirculated by a pump. Then the pH was brought to 7 to 8 by addition of6.0 g of disodium hydrogenphosphate (dodecahydrate) and the mixture wascooled to 0° C. 3.1 g (80 mmol) of sodium tetrahydridoborate was addedby portions within 1 hour. The heterogeneous mixture was stirred for 4more hours at 25° C. and then filtered. The filtrate was extracted fivetimes with 50 ml of ethyl acetate each time and the extract wasdistilled in a vacuum after the solvent was distilled off. The yield was2.7 g (42.3 percent). The product had a boiling point of 86° to 87° C./1torr. The following data concerns the product:

[α]_(D) ²⁰ =+8.9° (c=5, methanol)

¹ H-NMR: (CDCl₃, 300 MHz) δ: 1.60-2.00 (m, 8H); 3.55-3.70 (m, 3H); 3.78(dd, J=8/7 Hz, 1H, H-C(1)); 4.02 (dd, J=8/6 Hz, 1H, H-C(1)); 4.20 (dddd,J=7/6/5/4.5 Hz, 1H, H-C(2)).

Content: 99.1 percent (GC)

EXAMPLE 17 (S)-2,2-diethyl-1,3-dioxolane-4-methanol from5,6-O-(1-ethylpropylidene)-D-isoascorbic acid

18.5 g of hydrogen peroxide (30 percent solution in water, 160 mmol) wasinstilled within 2 hours in a suspension of 4.0 g (40 mmol) of calciumcarbonate, 6.4 g (60 mmol) of sodium carbonate and 10.3 g of5,6-O-(1-ethylpropylidene)-Disoascorbic acid (95 percent, 40 mmol;produced according to Example 4) in 150 ml of water, and the temperatureby cooling was kept below 20° C. The heterogeneous mixture was stirredfor 2 more hours at room temperature and 45 minutes at 40° C. and, afteraddition of 2 g of activated carbon, was heated in for 1 hour to 85° C.The calcium oxalate formed and the activated carbon were filtered off,the filtrate was put into a beaker thermostated at 40° C. and adjustedto pH 6.5 with sulfuric acid and kept at this pH during electrolysis.Electrolysis was performed in a tube (d=3 cm) on 2 cathodes and 2 anodesof graphite (d=0.5 cm, l=7 cm) at 1.2 A and a total of 2.5 faraday/mol,and the solution was continuously circulated by a pump. Aftertermination of electrolysis, 6 g of disodium hydrogenphosphate(dodecahydrate) was added to bring the pH to 7 to 8. The mixture wascooled to 0° C. and mixed with 3.1 g (80 mmol) of sodiumtetrahydridoborate by portions within 2 hours. After this addition, itwas stirred for 4 more hours at 25° C. and then filtered. The filtratewas extracted five times with 50 ml of ethyl acetate each time and theraw product, obtained from the extract, after the solvent was distilledoff, was distilled in a vacuum. The yield was 2.45 g (38.3 percent). Theproduct had a boiling point of 58° to 61° C./0.2 torr. The followingdata concerns the product:

[α]_(D) ²⁰ =+13.6° (c=5, methanol)

¹ H-NMR: (CDCl₃, 300 MHz) δ: 0.93 (t, 3H); 0.95 (t, 3H); 1.65 (q, 2H);1.69 (q,

2H); 2.17 (s, 1H, OH); 3.61 (dd, J=11/5 Hz, 1H, H-C(3)); 3.74 (m, 1H,H-C(3)); 3.75 (dd, J=8/7 Hz, 1H, H-C(1)); 4.03 (dd, J=8/7 Hz, 1H,H-C(1)); 4.23 (m, 1H, H-C(2)).

Content: 98.7 percent (GC)

EXAMPLE 18 (S)-2,2-dimethyl-1,3-dioxolane-4-methanol from5,6-O-isopropylidene-D-isoascorbic acid.

Analogously to Example 12, the (S)-2,2-dimethyl-1,3-dioxolane-4-methanolwas produced form 5,6-O-isopropylidene-D-isoascorbic acid by oxidationwith hydrogen peroxide in the presence of calcium carbonate and sodiumcarbonate and then electrolysis. The yield was 58.2 percent. The producthad a boiling point of 75° to 78° C./12 torr. The following dataconcerns the product:

[α]_(D) ²⁰ =+11.5° (c=5, methanol)

[α]_(D) ²⁰ =+15.1° (neat)

¹ H-NMR: (CDCl₃, 300 MHz) δ: 1.39 (s, 3H); 1.46 (s, 3H); 2.32 (s, 1H,OH); 3.61 (dd, J=11.5/5 Hz, 1H, H-C(3)); 3.74 (dd, J=11.5/4 Hz, 1H,H-C(3)); 3.80 (dd, J=8/6.5 Hz, 1H, H-C(1)); 4.04 (dd, J=8/6.5 Hz, 1H,H-C(1)); 4.25 (tdd, J=6.5/5/4 Hz, 1H, H-C(2)).

EXAMPLE 19 (R)-4-isopropylaminomethyl-2,2-dimethyl-1,3-dioxolane from5,6-O-isopropylidene-L-ascorbic acid

A solution of (S)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (amount andperformance as in Example 12, but without reduction with sodiumtetrahydridoborate) produced according to Example 12 was instilledwithin 3 hours under a hydrogen atmosphere in a mixture of 20 mlisopropylamine, 2.0 g of palladium/activated carbon (10 percent Pd) and200 ml of methanol. The mixture hydrogenated in a shaking apparatus at 3bars of hydrogen pressure and room temperature to the termination of thehydrogen absorption. Then the catalyst was filtered off and the filtratewas concentrated to 100 ml by evaporation. After addition of 10 g ofsodium carbonate the mixture was extracted five times with 50 ml ofdichloromethane each time, the dichloromethane phases were dried onsodium sulfate and the solvent was distilled off. The oily residue wasthen distilled in a vacuum. The yield was 6.8 g (41.4 percent, relativeto 5,6-O-isopropylidene-L-ascorbic acid). The boiling point was 43° to45° C./0.1 torr. The product had the following property:

[α]_(D) ²⁰ =+7.3° (c=2, methanol).

What is claimed is:
 1. Process for production of enantiomer-free 2,2,4trisubstituted 1,3-dioxolanes of the general formula: ##STR8## wherein R¹ and R² are either the same and are (a) hydrogen or(b) alkyl groups with 1 to 4 C atoms or (c) aryl groups or (d) arylalkyl groupsor R¹ and R² together are a 1,4-butanediyl or 1,5-pentanediyl group, and X is either a hydroxy group or, with the assumption that R¹ and R² are not aryl groups, NHR³ wherein R³ is alkyl with 1 to 8 C atoms or aryl, characterized in that (a), depending on the desired configuration, a corresponding substituted threonic acid or erythronic acid of the general formula: ##STR9## or a salt thereof is converted by electrolysis into the correspondingly substituted 1,3-dioxolane-4-carbaldehyde of the general formula: ##STR10## and (b), the corresponding substituted I,3-dioxolane-4-carbaldehyde, without being isolated is converted by reduction or reductive amination into the enantiomer-free 2,2,4-trisubstituted 1,3-dioxolane according to formula I.
 2. Process according to claim 1 wherein electrolysis is performed in an aqueous solution at pH 4 to
 10. 3. Process according to claim 2 wherein the electrolysis is performed in the presence of a tertiary amine.
 4. Process according to claim 2 wherein the threonic acid or erythronic acid is used in the form of an alkali or alkaline-earth salt.
 5. Process according to claim 4, wherein the threonic acid or erythronic acid is produced by the oxidative degradation of a correspondingly substituted ascorbic acid or isoascorbic acid of the general formula: ##STR11## with aqueous hydrogen peroxide in the presence of calcium carbonate.
 6. Process according to claim 5 wherein the oxidation of the ascorbic acid or isoascorbic acid takes place in the presence of an alkali carbonate.
 7. Process according to claim 1 wherein the electrolysis is performed in the presence of a tertiary amine.
 8. Process according to claim 1, wherein the threonic acid or erythronic acid is used in the form of an alkali or alkaline-earth salt.
 9. Process according to claim 1 wherein the threonic acid or erythronic acid is produced by the oxidative degradation of a correspondingly substituted ascorbic acid or isoascorbic acid of the general formula: ##STR12## with aqueous hydrogen peroxide in the presence of calcium carbonate.
 10. Process according to claim 9 wherein the oxidation of the ascorbic acid or isoascorbic acid takes place in the presence of an alkali carbonate.
 11. Process according to claim 1 wherein, in formula I, X is a hydroxy group and, in step (b), the conversion is achieved by reduction.
 12. Process according to claim 1 wherein, in formula I, X is NHR³ and, in step (b), the conversion is achieved by reductive amination. 